A baglike container has conventionally been used so as to transfer, mix or separate a liquid pharmaceutical or solution. For example, a so-called soft bag, that is a baglike container containing a medicinal liquid for administering an intravenous drip to a patient, is used as a container for a drip. A so-called double bag is also used that is a baglike container in which two or more kinds of medicinal liquids are separately sealed in one baglike container having at least one partition so that the partition is broken immediately before use and the medicinal liquids are mixed and then intravenously fed as a drip to the patient. There is also a blood bag including a plurality of baglike containers in which collected blood is separated into respective components and accommodated in a plurality of containers, and then the separated components can be administered to another case patient.
In addition, this kind of baglike container is variously employed so as to handle a liquid pharmaceutical or solution.
The reason is as follows. Namely, since an internal volume of a baglike container can vary according to the amount of a content liquid, it is necessary to promote filling and discharge of the content liquid by discharging air in the container or feeding air into the container when filling or discharging the content liquid. However, the container described above has a feature that it can fill or discharge the content liquid trough an attached port or a tube connected to the port. This feature makes it easy to realize a so-called closed system that enables execution of the above operation without causing contact of the content liquid with the open air, namely, execution of the operation without contamination of the content liquid with microorganisms from the open air. Therefore, this kind of the container is suited for use as a container for handling a liquid pharmaceutical collected and produced aseptically.
For these reasons, it is often preferred to employ a baglike container as a container which is required to have sterility. A baglike container is also employed as a container required to have sterility and requiring a centrifugal operation. The blood bag is one example thereof.
Namely, the blood bag as a baglike container filled with blood, as a dispersion liquid in which dispersoids such as red blood cells, white blood cells and blood platelets are dispersed in a dispersion medium such as blood plasma, is centrifuged to thereby separate blood in the container into components such as red blood cells, white blood cells, blood platelets and blood plasma, that are then transferred to and filled into separate baglike containers and then administered on a component to component basis to a plurality of patients.
Since the blood bag is used for the purpose of separating and recovering each component of the dispersion liquid, centrifugation is conducted by disposing a baglike container containing blood as the dispersion liquid, in a lengthwise centrifugal cup having a small floor area, with the port side upward and the bottom side downward.
In such a case, the container wall located under the liquid level formed on the surface of the dispersion liquid by a centrifugal force closely adheres to the inner face of a centrifugal adapter and does not further expand outwardly. As a result, tension is scarcely generated along the wall surface of the container wall and thus bag tearing and pinholes are not easily caused by centrifugation.
However, when a container is required to have sterility and requires a centrifugal operation, and is used for the purpose of not only separating the dispersion liquid into each component through centrifugation, for example, but also introducing a gene into target cells, dispersoids such as target cells and a vector are sedimented by centrifugation so as to be uniformly dispersed on a floor face of the container to thereby provide an environment that facilitates contact between the target cells and the vector, and, thus, a gene transfer efficiency is improved (see, for example, Patent Documents 1 and 2). A small floor area causes stacking of target cells upon centrifugation or contacting, which leads to a poor contact efficiency between the target cells and the vector and a poor gene transfer efficiency. Therefore, it is necessary to increase the floor area so that target cells can coexist in the uniform and scattered state without stacked on the floor face.
By conducting this operation on a floor face coated with a protein having high affinity for both the target cells and the vector, a contact efficiency between the target cells and the vector can be improved and also a gene transfer efficiency can be improved. Also in this case, when target cells become stacked, some cells cannot be contacted with the floor face coated with a protein, which leads to a poor gene transfer efficiency. Therefore, it is necessary to increase the floor area so that the target cells are dispersed without stacked on the floor face.
In order for a baglike container to satisfy these conditions during centrifugation, there is conducted an operation that a baglike container is laid on an adapter of a centrifuge having a large floor area, namely, a container wall surface of the baglike container is disposed in parallel to a floor face of the same adapter and centrifugation is conducted so as to apply a centrifugal force perpendicular to a container wall surface.
As a matter of course, when the container wall surface of the baglike container is coated with a protein having high affinity for both the target cells and the vector, the baglike container is disposed so that the protein-coated container wall surface of the baglike container functions as the floor face upon centrifugation.
Upon such the centrifugation, a centrifugal force to be applied on a content liquid in the baglike container, namely a culture medium, is converted into a pressure, while a force is produced expanding the container wall of the baglike container in the direction perpendicular to the floor face. However, it is impossible to expand the container wall of the baglike container in the direction perpendicular to the floor face as a result of obstruction with the floor face by the adapter. In contrast, a force capable of expanding in the direction parallel to the floor face is generated and thus both sides of the baglike container are exposed to a pressure load. Usually, this portion corresponds to the seal portion of the baglike container and may result in bag tearing as a result of seal peeling or breakage upon sealing. In particular, when only a weak seal strength is obtained like the case of sealing container walls each being composed of a different material, bag tearing may arise more easily.
In a baglike container containing cells requiring proliferation or activation during or after a centrifugal operation, culturing performance may be further improved, in some cases, by using different materials in the container wall of the floor face and the container wall of the ceiling. In this case, since different materials produce a seal, a seal having a strong seal strength is not necessarily obtained.
For example, this includes, the case where a material having affinity for cells is selected as a material constituting the container wall of the floor face, and a material having gas permeability is selected as a material constituting the container wall of the ceiling.
[Patent Document 1] U.S. Pat. No. 5,648,251
[Patent Document 2] International Publication No. WO 00/01836